In separation sciences, many commercial instruments utilize polymer coated fused silica capillaries, with bare glass bore surfaces or with coated bore surfaces (WCOT or wall coated open tubular) and packed columns. The most common fused silica capillaries used, such as in capillary GC, are coated (buffered) with a polyimide and having bore dimensions from approximately 0.15 mm to 1.00 mm, outer diameters (polymer) from approximately 0.25 mm to 1.25 mm, and lengths from several meters to one hundred meters. In CE and related techniques, capillary LC and capillary HPLC, capillary bores range from approximately 0.002 mm to 0.200 mm with outer diameters of 0.150 to 0.375 mm and are used in lengths from a few centimeters up to a meter. Capillaries may also find applications in “micro-plumbing” for manipulating very small samples.
Much of separation sciences is based upon differential partition of compounds in mixtures of liquids, vapors or gases between the “mobile phase” and “stationary phase” within the capillary column. Components in a mixture that adhere, adsorb or absorb less readily in stationary phase are transported more rapidly along the column than are components that are strongly absorbed, adhered, dissolved or otherwise bound to the stationary phase.
In capillary electrophoresis and some related methods, capillaries need not be coated or packed to effect separations as the mechanism of separation is based upon mass and charge and/or tertiary structure of the species in the mixture, typically macromolecules, but coatings and packed columns do offer additional specificity and control of mobility mechanisms and conditions. In liquid chromatography, separations based upon partitioning between stationary and mobile phases is the rule, but with liquid mobile phase and solid or liquid stationary phase, additional partitioning mechanisms may be exploited, e.g., antibody affinity. In gas chromatography, as a rule, separations are based upon differential partitioning between a stationary liquid phase and a mobile, inert gas phase.
These common techniques and more esoteric separation and concentration schemes exploit fused silica capillary as column base material, owing to the relatively low cost, high tensile strength and flexibility and generally inert chemical character of the material. While a boon for advancing separation techniques in speed, resolution and ability to handle extremely small samples, fused silica capillary does present several problems and limitations. Problems in silica capillary separations are myriad and differ somewhat depending upon the technique in question. Some examples of these problems are the necessity to tightly coil long columns in or on cages for handling and mounting in instrument ovens, upper processing and use temperature limits imposed by the polymer buffers' liability to oxidation, irreproducible sample loading in tiny capillary bores, fragility of on-column detection windows (devoid of polymer protection), lack of efficient and convenient interface with larger scale laboratory glassware and instruments and limited available surface area and tortuosity in the smooth bore.
In GC, many separations are performed with temperature programs wherein the entire column is raised in temperature over time to aid in eluting sequentially less volatile compounds. Efforts to speed such separations, where temperature program cycles may require over an hour to complete, depend upon the ability to raise and lower column temperatures more rapidly and also upon the upper temperature limit of the column. While stationary phase polymers capable of transient temperatures above 400° C. do exist, the buffer coatings that protect the flexible capillary generally degrade beginning at about 350° C., effectively limiting the upper use capacity of capillary columns. In addition, some processes used to modify the bore surface for binding stationary phase are less effective than they could be due to the sub optimal upper use and processing temperature limit of commercial fused silica capillary. A silica capillary column that is rugged enough for general handling without requiring polymer buffers has the distinct advantage of having upper use limits higher than any known column treatment process requirement or polymer stationary phase degradation temperature. Current means of circumventing the upper use temperature limit involve use of metal-coated silica capillaries, with limited success and practicality.
Additionally, the current ubiquitous coils of capillary within the column oven make differential column heating along the axis impractical: the entire column is at the same temperature at the same time. Additional separations may be addressed or current separations may be accelerated or resolution improved if columns could be held or ramped at different temperatures along the separations axis.
Column heating and cooling is currently inefficient and slow, owing to the necessity of heating and cooling the entire oven volume as opposed to the relatively small column volume. Developments have recently been made in reducing this problem, e.g. heating the capillary coating by radio frequency energy (RF), direct electric heating via a resistive heating element wound about the capillary length, but all have limitations and increased costs associated with them. U.S. Pat. No. 4,116,836 issued to DeAngelis discloses a packed monolithic hollow cylinder column of generally standard scale, with a helical or sinusoidal path within a cylinder wall, formed by fusion of compound glasses about a sacrificial mandrel or through fusion of plates with aligned channels. While interesting and likely of some value, this large monolithic approach to the problems of silica capillary in GC remains massive and extremely costly to produce.
Increasing the bore surface area in capillaries, upon which to immobilize stationary phase, benefits efficiency (as measured by speed or resolution or height equivalent to theoretical plate) but most means of increasing bore surface area also degrade performance by increasing eddy diffision (turbulent mixing). Any means whereby surface area might be increased without adversely increasing diffusion or restricting flow improves efficiency.
In other techniques, such as purification of proteins by capillary affinity chromatography, turbulent flow of the liquid mobile phase aids in insuring contact with target compound-specific wall coatings in relatively short interaction lengths, aiding efficiency. Some researchers adhere to the practice of tightly coiling capillary columns to impart turbulent flow within the liquid channel, insuring better probability of contact between target species and the coating. But tightly coiling capillary leads to new problems such as physical column containment and column fracture due to excessive bend stress (compression and tension) and the minimum radii to which it is practical to coil capillary are quite limited, e.g. a 200 μm inner diameter by 330 μm glass outer diameter capillary cannot safely be coiled tighter than a diameter of approximately 3.3 centimeters such that the maximum angle circumscribed by a centimeter of capillary is approximately 42°. A capillary that could offer higher tortuosity and/or turbulent flow without high stress would be a great advantage, for improved efficiency as well as for compaction to enable address of all wells of a microtiter plate (MTP) simultaneously, for example.
Much research and development has been performed in production and use of “lab-on-a-chip” type technologies in recent years. Devices encapsulating channels within polymer or glass monoliths are provided as alternatives to cylindrical capillary, for considerations of space and speed and for providing multi-dimensional separations, selectable on-column sample “loops” and ease if interface to optical and electrochemical detection schemes. These wafer-based, planar technologies suffer from difficulty in sample loading and recovery—often referred to as “real-world interface” problems—and are typically costly to produce, particularly in small production runs. Planar devices are rarely made of silica, even though silica is extremely attractive for optical and chemical properties, because of the great difficulty and cost of patterning and fusing layers of silica. By providing such micro-fluidic circuits on cylindrical substrates or monoliths, patterning and fusion are greatly simplified and standard, or slightly modified, flexible capillary interface schemes are compatible with cylindrical “lab-on-a-chip” technology. Several orders of magnitude in cost reductions and increased speed in analyses are possible with the disclosed technology.
Beyond the more obvious surface area to volume ratio alterations provided by multilumen silica capillary, additional applications, ranging from photonic bandgap-based waveguides (so-called photonic crystals) to filters are possible that may better be addressed in direct laser formation rather than draw of large preformed structures (preforms). The dimensional reduction ratios of freely drawn glass products limit possible dimensions in products produced and free draw is highly inefficient for low volume production.